The syngeneic mixed lymphocyte reaction (SMLR) is a measure of proliferation of T cells cultured with autologous or syngeneic non-T cells. SMLR is present in normal mouse strains but is absent in the autoimmune NZB strain. In the past year, we have found that: 1) the responder cell is in the Lyt 1 plus 2 minus 3 minus T cell subset, 2) SMLR occurs via Ia antigen, 3) two types of suppressor cells can be recovered from SMLR cultures; one is sensitive to pretreatment of mice with cortisone, the other is not, 4) the absence of SMLR and the presence of anti-thymocyte antibody in NZB mice are not genetically linked. In the next year, we will: 1) continue evaluating function of cells recovered from SMLR cultures by testing their effect on responses to T dependent and T independent antigens and to examine suppression by adoptive transfer experiments, 2) fully characterize the stimulator cell utilizing antisera to Lyb alloantigens and the fluorescence-activated cell sorter, 3) determine whether the SMLR defect in NZB mice is due to a defect at the T or the B cell level, 4) continue the genetic analysis of various manifestations of autoimmunity using the NZB x C58 recombinant inbred lines.